The Ambien effect-in graphs

[StillAnotherGuest]

I would say you respond quite strongly to Ambien. So much so that I would offer than it was the major contributor to the long length of those central apneas during your titration:



However, I do not believe that the mechanism was the one that one usually associates with pharmacologically-induced breathing issues, namely, respiratory suppression and central hypoventilation (breathing just sorta stops, both rate and depth)-- rather, the central apneas were initially chemoreflex-dependent in nature, however, the Ambien suppressed your arousal threshold, such those central apneas were not terminated by the normal mechanisms and were allowed to persist far longer that they should have. Indeed, most of those centrals were not terminated by arousal.

I also think these two phenomena (appearance of central apnea, length of central apnea) must be considered independently. If we believe that CompSAS will subside with traditional CPAP over time (the body simply gets acclimated with PAP Therapy), then it may be that you simply no longer have a tendency to have central apnea, so the decreased arousal threshold leading to increased apnea length becomes academic.

Interestingly, the use of Ambien is often indicated to help CompSAS in that it reduces the excess chemoresponsiveness associated with CompSAS. This too, then, may only need to be to be done during the acclimatization period. After that, it's use becomes more conventional, e.g., it improves sleep.

So again, it would appear now that your CompSAS is stable on traditional PAP, and that aggressive IPAP attack is simply responding to Wake/Stage 1, revealing the major shortcoming of ASV, namely, it's inability to adjust to that transition state. The Ambien stabilizes your sleep and thus calms the AutoSV. If this is so, then we're back to considering the use of fixed CPAP.

SAG

[slapmeawake]

Bev, I think the more important issue here is the hot flashes because I think they could be and important clue as to why you aren't sleeping. I am going through similar experiences that started a year ago. I think my sleep issues now are hormonal, as I have gone through menopause also. when I started on cpap two years ago I did great. Slept 6 to 7 straight hours. Now for the past year sleep is fractured again. Been having menopause symptoms too and one is sleep issues. when I get the migraine or heart palpitations, I call that my hormone burst. On those days when I have the symptoms I sleep much better, almost like I'm getting a little bit of extra estrogen. So maybe you can discuss it with the gynecologist and see what he says. Hormones are a terrible thing lol!!!!!!!!! They should invite a gyno to our next Awake meeting for us ladies going through menopause and having sleep issues. Oh, and that woman at the meeting from Manors name is Debbie Shirley, I found her card. I have to get over there to see the new supplies. Carol

[Violet]

Bev,
Sorry I'm not knowledgeable enough to read or remark on your charts.

But you mentioned: "I struggled for well over an hour with almost getting there and then becoming fully awake again." Even when my hormones were behaving, this would go on all night for me. The only way I could stay asleep was to have a fan directly facing the bed creating a constant cool air circulation to breath, even during Winter and Summer with air condtioning. And now with CPAP, I still need the cool air circulation but now just circulating around my head. There is no way I can stay asleep without air circulation.

Right now I'm taking the generic IC Zolpidem Tartrate 5 mg and I don't wake up till the alarm at 4:30 a.m. Last week my sleep dr told me "to continue it for the next couple of months. Let it help me become more rested and feeling better, then I can start on weekends to see how it feels without taking it." I always take it an hour before I expect to sleep.

[OutaSync]

SAG,
Every time I see that snapshot of my hypnogram I am reminded why I have to keep on with this even though it seems so counterproductive. Question: If my centrals were not terminated by arousal, what terminated them? That is what scared me enough to get the SV. At least I know that if I stop breathing for 12 seconds, it will nudge me to breathe. I know it does because sometimes I wake up with it kinda breathing for me. I don't mind a trial of running at straight CPAP as long as it's on this machine with a set back up rate. It seems as though we tried that way in the beginning, but I can't remember the outcome.

Kiralynx, slapmeawake and Violet,

I really don't think that my "hot flashes" are hormonal in nature because I have had them all of my life. THey are probably more stress induced. I get them when I'm under stress for anything at all, even getting dressed in the morning always breakes me out in a sweat. Until the OSA diagnosis, I couldn't figure out what was stressing me out during my sleep. The above posted graph explains it, and I'll always be grateful to SAG for showing that to me at the point when I was too tired to be making decisions for myself.

Bev

[StillAnotherGuest]

If my centrals were not terminated by arousal, what terminated them?

9 times out of 9, a central apnea will be terminated when the increasing pCO2 from not breathing rises above the apnea threshold and the drive to breathe resumes (so it makes more sense conceptually to consider that it is breathing that resumes vs apnea terminates). Now, the reason that one got into the central apnea fix in the first place is that hyperventilation caused by the arousal (overshoot caused by increased chemoresponsiveness) drove the pCO2 below the apnea threshold, causing the central apnea. Then the whole mess gets cyclical and repeats ad infinitum.

In addition, drug effect can increase the length of apneas, which is what I believe happened to an extent in your case, and that in turn caused those terrific desaturations. And I think we should stick with "to an extent", because there were still plenty of significant respiratory events later those nights when one would have thought that the Ambien effect should have largely worn off.

Also, it just goes to show that you really can't depend on hypoxic drive to do much for you during sleep.

So, in central apnea and CompSAS, it is the arousal that is the root of all evil! In fact, Magdy Younes points out to us that you really don't need an arousal to terminate an obstructive event either!

BTW, you had some (many, actually) really outstanding mixed apneas (good specimens can be difficult to find). Mind if I show a couple?

Reminder: CompSAS may simply improve/resolve on its own, given time. I believe that your persistence in therapy has made your breathing a lot more stable than it was in those studies.

Speaking of which, time for a new study (See? I waited two posts!) I thought we were going to take a closer look at the possibility of N. being in there.

SAG

[OutaSync]

SAG,

You may share with our group any examples from my sleep study that you wish to. Teach us, please! If you want to revive the old thread so people can have the background, that would be fine, too. I think that I am in better mental condition( 19 months on XPAP) to understand things now, but you may need to dumb it down just a little.

Are you thinking that the aggressive IPAP is causing some of my arousals and putting me in the downward spiral? Now that I 've acclimated (sort of) to this machine, I can try staight APAP, again? Straight 14? 16?

A couple of things have kept me from a third study. I don't trust my sleep doctor. He said I was fine and to come back in a year. I don't know how to find a better doctor, since he came from an accredited center. How does one know in advance if a doctor is going to be any good? I'm not sure if I could make it through a study without the Ambien, and I wanted to get a drug-free study, as a comparison.

To test for narcolepsy requires daytime naps. I don't think I could relax enough to nap in a sleep center.

Bev

[-SWS]

Bev, I recall that your cortisol levels tested high on your thyroid panel. That's usually indicative of stress or malfunctioning adrenal production. Regardless, if your cortisol levels are frequently sustained, perhaps that explains your awakenings and all that night-to-night cardiopulmonary variability:

http://www.lightningitcorp.com/ehc/pdf/ ... _sleep.pdf

Although the link between a stressful day and a restless night is well known, in a study funded by the
National Institute of Mental Health, scientists continued to search for the exact ways that stress affects sleep.
A new study suggests that stress may disrupt the nervous system’s natural rhythms during various sleep stages.
Stressed sleepers experience more arousal during sleep, Martica Hall, Ph.D. of the University of Pittsburgh and
colleagues write in the journal Psychosomatic Medicine. Sleepers who were less relaxed during sleep also woke
up more often and had fewer episodes of deep sleep, according to the researchers.

Hall and colleagues measured the central nervous system changes by monitoring heart rate variations and noted
that certain heart rate variations provided an indirect glimpse into the activity of the involuntary nervous system,
which directs the function of organs like the heart and lungs. It was noted by Hall and his colleagues that Insomniacs
have heart rate variability patterns similar to those seen in the stressed students, which may suggest that similar
pathways of nervous system disruption are at work during the period of sleeplessness. The study was funded
by the National Institutes of Mental Health.

I think your elevated cortisol levels just may explain your perplexing daytime pulse oximetry results as well (once again
plausibly presenting erratic cardiopulmonary variability).

In summary: I get the impression that elevated stress and/or cortisol levels just may explain Bev's frequent awakenings
and even cardiopulmonary variability (dare I say "bifurcation"). There! I said it! Even if in parentheses!

SAG, if elevated cortisol happens to be Bev's outstanding sleep issue, is that biochem problem likely to come in under radar
during a typical NPSG? And if that really is at the heart of Bev's sleep-maintenance and central-nervous system variability, how
might Bev best go about having that kind of health problem diagnosed and treated? Thanks.

P.S. Might Ambien have partially mitigated a cortisol or stress problem at night in this particular case?

[Kiralynx]

Kiralynx,

I would love to see how your charts compare to mine.

Bev,

Here they are.

viewtopic/t40856/Then-and-Now-3-Charts.html

Separate thread, so I don't hijack yours.

[ozij]

Reminder: CompSAS may simply improve/resolve on its own, given time. I believe that your persistence in therapy has made your breathing a lot more stable than it was in those studies.

Any idea of how much time, SAG? Or, put differently: how much time would you give it? What (other than success) would make you decide to stop the acclimatization trial?


O.

[StillAnotherGuest]

Reminder: CompSAS may simply improve/resolve on its own, given time. I believe that your persistence in therapy has made your breathing a lot more stable than it was in those studies.

Any idea of how much time, SAG? Or, put differently: how much time would you give it? What (other than success) would make you decide to stop the acclimatization trial?

These guys looked at 2 to 3 months:

The Significance and Outcome of Continuous Positive Airway Pressure-Related Central Sleep Apnea During Split-Night Sleep Studies

Nearly all patients with CPAP-induced CSA at baseline had complete resolution of the central events on follow-up when studied on the prescribed level of CPAP used to eliminate OSA. The patients were studied on the same effective pressure for the obstructive apnea that was determined on the first night of sleep study. Our findings suggest that CPAP-related CSA may be explained by ventilatory control instability resulting from sleep fragmentation as demonstrated by decreased SE, increased sleep stage 1, WASO, and arousals in the study group during the baseline study. These central respiratory events were consistently eliminated or significantly reduced on follow-up polysomnography, and this was associated with a significant improvement in total sleep time, as well as reduced light sleep and total arousals. This could be attributed to a progressive improvement in the hypercapnic ventilatory response, as OSA patients treated with CPAP, have improved sleep quality, fewer sleep state transitions, and eventually more restorative sleep.

CPAP-related CSA appears to represent a benign and transient phenomenon and is likely related to sleep fragmentation and sleep stage shifts that occur with initial CPAP titration. Bilevel positive airway pressure (BPAP) is often used in the treatment of Cheyne-Stokes respirations in patients with CHF and is frequently considered as an alternative mean to treat CSA events occurring during CPAP titration. However, reports have suggested that BPAP may actually worsen CSA with or without periodic breathing mediated by an overshoot in ventilation causing decreased Pco2 below the apneic threshold. Treating CPAP-induced central apnea with BPAP could also carry the potential of worsening these self-limited events. Finally, the persistence of CSA despite adequate CPAP therapy may warrant further investigation for occult cardiovascular disease. Larger prospective studies are needed for assessing the incidence and prevalence of CHF in patients with sleep-disordered breathing, in particular CSA.

and put up a graph that I think dramatically emphasizes this point, where CSA events drop precipitously:

if elevated cortisol happens to be Bev's outstanding sleep issue, is that biochem problem likely to come in under radar during a typical NPSG? And if that really is at the heart of Bev's sleep-maintenance and central-nervous system variability, how might Bev best go about having that kind of health problem diagnosed and treated?

She needs another sleep study, because although the original studies are fascinating, at this point they are quite dated and undoubtedly bear no resemblance to where she's at now. For instance, your comments imply that she has insomnia, but despite sub-optimal sleep efficiencies in the titration PSGs (82.6% and 83.4%), there was no sustained control of respiratory events and consequently can not be used to determine baseline. Although she currently complains of frequent awakenings, is her overall sleep efficiency at an acceptable level? Is there another medical issue underfoot (like N.)? Is she another victim of poor sleep efficiency associated with being female? Did that laundry list of medications/supplements contribute to poor sleep architecture?

Are you thinking that the aggressive IPAP is causing some of my arousals and putting me in the downward spiral?

You've got one night there ("the good night") on essentially straight 13 cmH2O, and another ("the bad night") on basically BiLevel 18/13 cmH2O. I believe that:

1. Ambien helps your overall sleep quality, decreasing your arousal threshold (does it ever!) and wake time;
2. It is the arousals and Wake/N1 transitions that cause the aggressive IPAP attack, not the other way around;
3. This upsets the concept of acclimatization;
4. Arbitrary dial wingin' is bad (I know you don't do that, Bev, but I haven't said that lately, and this is as good a segue as any); and
5. Way back at the birth of ASV SAG said don't go crazy with this technology because the number of true qualifiers would be small (ASAA has more moderators than SAG has ASV patients).

SAG

[-SWS]

if elevated cortisol happens to be Bev's outstanding sleep issue, is that biochem problem likely to come in under radar during a typical NPSG? And if that really is at the heart of Bev's sleep-maintenance and central-nervous system variability, how might Bev best go about having that kind of health problem diagnosed and treated?

She needs another sleep study, because although the original studies are fascinating, at this point they are quite dated and undoubtedly bear no resemblance to where she's at now. For instance, your comments imply that she has insomnia, but the original PSGs did not suggest that. Although she currently complains of frequent awakenings, is her overall sleep efficiency at an acceptable level? Is there another medical issue underfoot (like N.)?

I absolutely agree that Bev needs another sleep study. No argument. She really needs another sleep study.

But your last point about questioning whether there are one or more outstanding medical issues gets at my two rhetorical questions about her measured cortisol levels: 1) don't Bev's awakenings and central-nervous system variability symptomatically correlate with her high cortisol levels, and 2) if elevated cortisol just so happens to be at the heart of Bev's outstanding symptoms, doesn't she need additional biochemistry medical work that extends beyond the scope of today's typical PSG screening and diagnosis?

I'm thinking that elevated cortisol levels probably fit Bev's daytime symptoms of fatigue as well. While she needs a sleep study to test for the possibility of N, she would in all likelihood presents atypically for N, even during an MSLT. So that begs the question of what a combination of N and elevated cortisol levels might symptomatically present as...

I would contend that N patients with pathologically-elevated cortisol levels would present as a test-sensitivity statistical outliers for typical N/MSLT test suite----and that patients with pathologically-elevated cortisol levels having no N can easily stay undiagnosed/misdiagnosed without further biochemical testing.

I'm not saying that Bev's elevated cortisol levels are a problem. But I am saying that they potentially corroborate every one of her outstanding symptoms, and may warrant a closer look. She absolutely needs another sleep study as well. But if it were me I'd have a closer look at that elevated cortisol level as well.

[StillAnotherGuest]

But your last point about questioning whether there are one or more outstanding medical issues gets at my two rhetorical questions about her measured cortisol levels: 1) don't Bev's awakenings and central-nervous system variability symptomatically correlate with her high cortisol levels, and 2) if elevated cortisol just so happens to be at the heart of Bev's outstanding symptoms, doesn't she need additional biochemistry medical work that extends beyond the scope of today's typical PSG screening and diagnosis?

How many cortisol levels do you plan on doing, and at what time(s) of day?

SAG

[-SWS]

SAG, I don't know to be perfectly honest. I'm asking that question as if I were the patient---not as if I were a clinician or doctor.

But restating my non-professional question another way: Can consistently-elevated cortisol or adrenal malfunction be responsible for Bev's outstanding symptoms of frequent awakenings and breathing variability?

Is Bev's elevated cortisol reading something that should justifiably be discarded at this point (as a typical secondary sleep-deprivation symptom)? Or might that elevated cortisol reading serve as a possible avenue of endocrinology or even CBT investigation for her somewhat atypical outstanding symptoms (with elevated cortisol more related to a different primary condition)? I realize that sleep deprivation and cortisol can have a two-way relationship: 1) sleep deprivation heightens cortisol, but 2) primarily heightened stress/cortisol can deteriorate sleep and central nervous function.

I think sleep clinic patients in general can present heightened cortisol levels as a secondary symptom of their sleep disorders. But I also think Bev's atypical outstanding symptoms just might be the result of heightened cortisol levels as symptomatic of a different primary problem (affecting both sleep and central nervous function). I suspect Ambien may partially mitigate some of the more primary cortisol-related etiologies as well.

I agree that a conventional sleep study w/MSLT is but one very logical next step. I think it is a necessary step as well.

[StillAnotherGuest]

Well, my point in the earlier question

How many cortisol levels do you plan on doing, and at what time(s) of day?

was that a single cortisol value (and I only saw Bev's value as being "very high") may not be very helpful in determining the relation to sleep. It would be better to create a 24-hour profile (hey, it ain't my money), since as you probably know, cortisol levels are cyclical in nature.

Here is a great graph showing the cortisol levels of insomniacs (squares) vs controls (circles) showing increased cortisol for like 6 hours in:

Chronic Insomnia Is Associated with Nyctohemeral Activation of the Hypothalamic-Pituitary-Adrenal Axis: Clinical Implications



SAG

[jnk]

. . . At least I know that if I stop breathing for 12 seconds, it will nudge me to breathe. I know it does because sometimes I wake up with it kinda breathing for me. I don't mind a trial of running at straight CPAP as long as it's on this machine with a set back up rate. . . .

Bev

This may be a silly idea (not my first), but, if it is being suggested that you try straight CPAP without a back-up rate, would your wearing a pulse-ox with an alarm make you more comfortable with the idea? Just a thought.